40064-34-4

Basic information

• Product Name: 4,4-Piperidinediol hydrochloride
• Synonyms: LABOTEST-BB LT00159431;4-PIPERIDONE HYDRATE HYDROCHLORIDE;4-PIPERIDONE HYDROCHLORIDE;4-PIPERIDONE HYDROCHLORIDE MONOHYDRATE;4-PIPERIDONE MONOHYDRATE HYDROCHLORIDE;4-PIPERIDONE MONOHYDRATE MONOHYDROCHLORIDE;4-PIPERIDINONEMONOHYDRATE HYDROCHLORIDE;4-AZACYCLOHEXANONE MONOHYDRATE HYDROCHLORIDE
• CAS NO: 40064-34-4
• Molecular Formula: C₅H₉NO*ClH*H₂O
• Molecular Weight: 153.61
• EINECS: 254-779-9
• Product Categories: Nitrogen cyclic compounds;Amines and Anilines;Carbonyl Compounds;Miscellaneous;Piperidine;Miscellaneous Reagents;Building Blocks;Heterocyclic Building Blocks;Piperidones;Building Blocks;Chemical Synthesis;Heterocyclic Building Blocks;Benzopyrans
• Mol File: 40064-34-4.mol

Chemical Properties

• Melting Point: 97-99 °C
• Boiling Point: 256.8 °C at 760 mmHg
• Flash Point: 147.9 °C
• Appearance: Off-white to yellow-beige/Crystalline Powder
• Vapor Pressure: 1.17mmHg at 25°C
• Storage Temp.: Store at 0-5°C
• Water Solubility: Soluble in water.
• BRN: 3916558
• CAS DataBase Reference: 4,4-Piperidinediol hydrochloride(CAS DataBase Reference)
• NIST Chemistry Reference: 4,4-Piperidinediol hydrochloride(40064-34-4)
• EPA Substance Registry System: 4,4-Piperidinediol hydrochloride(40064-34-4)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36-37/39
• WGK Germany: 3
• F: 3
• Hazardous Substances Data: 40064-34-4(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
4,4-Piperidinediol hydrochloride is used as a starting material for the synthesis of fentanyl (hydrochloride) with phenethylbromide. This application is particularly relevant in the development of potent analgesic medications.
Used in Research and Forensic Applications:
As an analytical reference standard, 4,4-Piperidinediol hydrochloride is utilized in research and forensic applications to study and identify the properties of related compounds.
Used in Chemical Synthesis:
4,4-Piperidinediol hydrochloride is used in the preparation of highly functionalized N-(Pyridinylmethyl)-bis[(E)-arylmethylidene]tetrahydropyridinones, which are important for crystal and molecular structure studies, as well as Density Functional Theory (DFT) investigations.
Used in Compound Library Generation:
4,4-Piperidinediol hydrochloride is employed in the generation of compound libraries based on sub-reactions of an Ugi multicomponent reaction (MCR). This application is significant for the development of new chemical entities and potential drug candidates.

InChI:InChI=1/C5H9NO/c7-5-1-3-6-4-2-5/h6H,1-4H2/p+1

Synthetic route

piperidin-4-one; hydrochloride sesquiethylate → 4-piperidone monohydrochloride monohydrate (40064-34-4)

Conditions	Yield
With hydrogenchloride; water

4-piperidone monohydrochloride monohydrate (40064-34-4) + phenoxyamine hydrochloride (6092-80-4) → 1,2,3,4-tetrahydro[1]benzofuro[3,2-c]pyridine hydrochloride (49540-52-5)

Conditions	Yield
With hydrogenchloride In isopropyl alcohol	100%

4-piperidone monohydrochloride monohydrate (40064-34-4) + trimethyl orthoformate (149-73-5) → 4,4-dimethoxypiperidine monohydrochloride (77542-16-6)

Conditions	Yield
With toluene-4-sulfonic acid In methanol at 20℃; for 22h;	100%

4-piperidone monohydrochloride monohydrate (40064-34-4) + trityl chloride (76-83-5) → 1-triphenylmethyl-4-piperidone (112257-60-0)

Conditions	Yield
With triethylamine In N-methyl-acetamide; water	98.3%
With triethylamine In N,N-dimethyl-formamide at 60℃; for 5h;	70.2%

di-tert-butyl dicarbonate (24424-99-5) + 4-piperidone monohydrochloride monohydrate (40064-34-4) → N-tert-butyloxycarbonylpiperidin-4-one (79099-07-3)

Conditions	Yield
With sodium hydroxide In 1,4-dioxane; water for 12h; Cooling with ice;	94%
With sodium hydroxide In 1,4-dioxane	92.5%
With triethylamine In dichloromethane; ethyl acetate	86%

4-piperidone monohydrochloride monohydrate (40064-34-4) + sodium carbonate (497-19-8) + 4-chloro-2-(trifluoromethyl)pyrimidine (1514-96-1) → 1-[2-(Trifluoromethyl)-4-pyrimidinyl]-4-piperidone

Conditions	Yield
In dichloromethane	92%

2-(thiophen-2-yl)ethyl methanesulfonate (61380-07-2) + 4-piperidone monohydrochloride monohydrate (40064-34-4) → N-[2-(2-thienyl)ethyl]-4-piperidinone (92065-14-0)

Conditions	Yield
Stage #1: 4-piperidone monohydrochloride monohydrate With N-benzyl-N,N,N-triethylammonium chloride; potassium carbonate In acetonitrile at 60℃; for 1h; Stage #2: 2-(thiophen-2-yl)ethyl methanesulfonate In acetonitrile at 80℃; for 24h; Reagent/catalyst;	90%

7-bromo-1H-indole (51417-51-7) + 4-piperidone monohydrochloride monohydrate (40064-34-4) → 7-bromo-3-piperidin-4-yl-1H-indole (312631-09-7)

Conditions	Yield
	89%

[1,1,2,2-(2)H4]ethane-1,2-diol (2219-51-4) + 4-piperidone monohydrochloride monohydrate (40064-34-4) → 2,2,3,3-tetradeutero-1,4-dioxa-8-azaspiro<4,5>decane (84376-17-0)

Conditions	Yield
In benzene for 48h; Heating;	88%

C16H15FO2 + 4-piperidone monohydrochloride monohydrate (40064-34-4) → 1-[2′-(2-fluoroethyl)-2-methylbiphenyl-4-carbonyl]-piperidin-4-one

Conditions	Yield
Stage #1: C16H15FO2 With 4-methyl-morpholine; 1-[(1-(cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylamino-morpholino)]-uronium hexafluorophosphate In N,N-dimethyl-formamide for 0.166667h; Cooling with ice; Stage #2: 4-piperidone monohydrochloride monohydrate In N,N-dimethyl-formamide at 0 - 20℃;	88%

1-amino-1,2,3,4-tetrahydroquinoline (5825-45-6) + 4-piperidone monohydrochloride monohydrate (40064-34-4) → 5,6,8,9,10,11-hexahydro-4H-pyrido[3',4':4,5]pyrrolo[3,2,1-ij]quinoline

Conditions	Yield
With hydrogenchloride	85%

1-amino-1,2,3,4-tetrahydroquinoline (5825-45-6) + 4-piperidone monohydrochloride monohydrate (40064-34-4) → 5,6,8,9,10,11-hexahydro-4H-pyrido[3',4':4,5]pyrrolo[3,2,1-ij]quinoline; hydrochloride

Conditions	Yield
With hydrogenchloride In ethanol for 3h; Reflux;	85%

2-methyl-1,2-pentanediol (20667-05-4) + 4-piperidone monohydrochloride monohydrate (40064-34-4) → 4-piperidone 2-propylpropyleneacetal

Conditions	Yield
With p-toluenesulfonic acid monohydrate In toluene	84%

4-fluoro-2-methoxy-1-nitrobenzene (448-19-1) + 4-piperidone monohydrochloride monohydrate (40064-34-4) → 1-(3-methoxy-4 nitrophenyl)piperidin-4-one (761440-64-6)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In acetonitrile at 80℃; Inert atmosphere;	84%

5-methoxylindole (1006-94-6) + 4-piperidone monohydrochloride monohydrate (40064-34-4) → 4-(5-methoxy-1H-indol-3-yl)piperidine (52157-82-1)

Conditions	Yield
	83%

4-piperidone monohydrochloride monohydrate (40064-34-4) + S-tert-butoxycarbonyl-4,6-dimethyl-2-mercaptopyrimidine (41840-28-2) → N-tert-butyloxycarbonylpiperidin-4-one (79099-07-3)

Conditions	Yield
With triethylamine In 1,4-dioxane; water for 6h; Ambient temperature;	81.3%

5-(bromomethyl)-2-(2-nitrophenyl)benzo[d]oxazole + 4-piperidone monohydrochloride monohydrate (40064-34-4) → 1-((2-(2-nitrophenyl)benzo[d]oxazol-5-yl)methyl)piperidin-4-one

Conditions	Yield
With acetic anhydride; potassium carbonate In acetonitrile at 20℃; for 5h;	81.2%

1H-indazol-5-ylamine (19335-11-6) + 4-piperidone monohydrochloride monohydrate (40064-34-4) + sodium hydrogencarbonate (144-55-8) + 1-chloro-2-(chloromethyl)benzene (611-19-8) → N-[1-(2-Chlorobenzyl)-4-piperidyl]-N-(1H-5 indazolyl)amine

Conditions	Yield
With potassium carbonate; acetic acid In methanol; acetonitrile	80%

1H-indazol-5-ylamine (19335-11-6) + 4-piperidone monohydrochloride monohydrate (40064-34-4) + sodium hydrogencarbonate (144-55-8) + 1-chloromethyl-4-fluorobenzene (352-11-4) → N-[1-(4-Fluorobenzyl)-4-piperidyl]-N-(1H-5-indazolyl)amine

Conditions	Yield
With potassium carbonate; acetic acid In methanol; acetonitrile	79%

1H-indazol-5-ylamine (19335-11-6) + 4-piperidone monohydrochloride monohydrate (40064-34-4) + sodium hydrogencarbonate (144-55-8) + 1-Chloro-3-chloromethyl-benzene (620-20-2) → N-[1-(3-Chlorobenzyl)-4-piperidyl]-N-(1H-5-indazolyl)amine

Conditions	Yield
With potassium carbonate In methanol; acetonitrile	79%

1H-indazol-5-ylamine (19335-11-6) + 4-piperidone monohydrochloride monohydrate (40064-34-4) + sodium hydrogencarbonate (144-55-8) + 1-Chloro-4-(chloromethyl)benzene (104-83-6) → N-[1-(4-Chlorobenzyl)-4-piperidyl]-N-(1H-5-indazolyl)amine

Conditions	Yield
With potassium carbonate; acetic acid In methanol; acetonitrile	79%

6-chloropiperonyl chloride (23468-31-7) + 1H-indazol-5-ylamine (19335-11-6) + 4-piperidone monohydrochloride monohydrate (40064-34-4) + sodium hydrogencarbonate (144-55-8) → N-{1-[(6-Chloro-1,3-benzodioxol-5-yl)methyl]-4-piperidyl}-N-(1H-5-indazolyl)amine

Conditions	Yield
With potassium carbonate; acetic acid In methanol; acetonitrile	78%

4-piperidone monohydrochloride monohydrate (40064-34-4) + 6-chloro-7H-purine (87-42-3) → 1-(purin-6-yl)piperidin-4-one

Conditions	Yield
With triethylamine In N,N-dimethyl-formamide at 50℃; for 2h;	77%

1H-indazol-5-ylamine (19335-11-6) + 4-piperidone monohydrochloride monohydrate (40064-34-4) + sodium hydrogencarbonate (144-55-8) + 4-Methylbenzyl chloride (104-82-5) → N-(1H-5-Indazolyl)-N-[1-(4-methylbenzyl)-4-piperidyl]amine

Conditions	Yield
With potassium carbonate; acetic acid In methanol; acetonitrile	76%

2-bromophenylhydrazine hydrochloride (50709-33-6) + 4-piperidone monohydrochloride monohydrate (40064-34-4) → 6-bromo-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole hydrochloric acid salt (1059630-11-3)

Conditions	Yield
With hydrogenchloride In ethanol for 6h; Reflux; Inert atmosphere;	76%

4-piperidone monohydrochloride monohydrate (40064-34-4) + 2,6-dichloro-7H-purine (5451-40-1) → 1-(2-chloropurin-6-yl)piperidin-4-one

Conditions	Yield
With triethylamine In isopropyl alcohol at 60℃; for 2h;	76%

1H-indazol-5-ylamine (19335-11-6) + 4-piperidone monohydrochloride monohydrate (40064-34-4) + sodium hydrogencarbonate (144-55-8) + 4-benzyloxybenzyl chloride (836-42-0) → N-{1-[4-(Benzyloxy)benzyl]-4-piperidyl}-N-(1H-5-indazolyl)amine

Conditions	Yield
With potassium carbonate; acetic acid In methanol; acetonitrile	75%

1H-indazol-5-ylamine (19335-11-6) + 4-piperidone monohydrochloride monohydrate (40064-34-4) + sodium hydrogencarbonate (144-55-8) + p-methoxybenzyl chloride (824-94-2) → N-(1H-5-Indazolyl)-N-[1-(4-methoxybenzyl)-4-piperidyl]amine

Conditions	Yield
With potassium carbonate; acetic acid In methanol; acetonitrile	74%

2-phenyl-indole (948-65-2) + 4-piperidone monohydrochloride monohydrate (40064-34-4) → 2-phenyl-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole (221109-25-7)

Conditions	Yield
With phosphoric acid In acetic acid; ethyl acetate	73%

1-amino-2,3-dihydroindole hydrochloride (92259-86-4) + 4-piperidone monohydrochloride monohydrate (40064-34-4) → 4,5,7,8,9,10-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole (313666-86-3)

Conditions	Yield
In isopropyl alcohol for 4h; Reflux;	73%

4-piperidone monohydrochloride monohydrate (40064-34-4) + 2,4-difluorobenzoyl chloride (72482-64-5) → 4-(2,4-difluorobenzoyl)piperidinone

Conditions	Yield
With triethylamine In dichloromethane	71%

Upstream product

• 41979-39-9 4-piperidone hydrochloride 

Downstream Products

• 34376-54-0 [1,4]diazepan-5-one 
• 79099-07-3 N-tert-butyloxycarbonylpiperidin-4-one 
• 132611-56-4 2-phenyl-1,2,4,8-tetraazaspiro<4.5>decan-3-one 
• 79098-55-8 3-<1-<2-(3,4-dimethoxyphenyl)-2-oxoethyl>-4-piperidylidene>-1,3-dihydro-2H-indol-2-one 
• 79098-62-7 3-{1-[2-(3,4-Dimethoxy-phenyl)-2-hydroxy-ethyl]-piperidin-4-ylidene}-1,3-dihydro-indol-2-one 
• 132611-57-5 8-benzoyl-2-phenyl-1,2,4,8-tetraazaspiro<4.5>decan-3-one 
• 397328-84-6 1-[4-(1H-pyrrol-2-ylcarbonyl)benzyl]piperidin-4-one 
• 218780-53-1 1-(methylsulfonyl)piperidin-4-one 
• 49540-52-5 1,2,3,4-tetrahydro[1]benzofuro[3,2-c]pyridine hydrochloride 
• 65347-55-9 3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole 
• 65220-86-2 1-(trifluoroacetyl)-4-piperidone 
• 149669-43-2 5-fluoro-3-(piperidin-4-yl)-1H-indole 
• 427886-14-4 1-[[2-(3,4,5-trimethoxyphenyl)pyridin-4-yl]methyl]-4-piperidone 
• 52157-82-1 4-(5-methoxy-1H-indol-3-yl)piperidine 

Relevant articles and documents

Using the electrostatic field effect to design a new class of inhibitors for cysteine proteases

A new class of competitive inhibitors for the cysteine protease papain is described. These inhibitors are based upon a 4-heterocyclohexanone ring and are designed to react with the enzyme active site nucleophile to give a reversibly formed hemithioketal. The electrophilicity of the ketone in these inhibitors is enhanced by ring strain and by through-space electrostatic repulsion with the heteroatom at the 1-position of the ring. Equilibrium constants for addition of water and 3-mercaptopropionic acid to several 4- heterocyclohexanones were measured by 1H NMR spectroscopy. These reactions model addition of the active site nucleophile to the corresponding inhibitors. The equilibrium constants give a linear correlation with the field substituent constant F for the functional group at the 1-position of the heterocyclohexanone. These equilibrium constants also correlate well with the inhibition constants for the 4-heterocyclohexanone-based inhibitors, which range from 11 to 120 μM. Thus, the model system can be used to predict the potency of structurally related enzyme inhibitors.